Trifluoroacetic acid → HCID 67123869, compound

Temperature

50 °C

The crude TFA salt of 5.67 (0.089 mmol) was taken up in THF (2 mL) and was treated with iPr2NEt (16 μL, 0.089 mmol), 3-oxetanone (29 μL, 0.45 mmol) and sodium triacetoxyborohydride (132 mg, 0.62 mmol). The resulting mixture was heated to 50° C. and was stirred for 3 h. The reaction mixture was then partitioned between DCM, water, and 5% (w/v) saturated aqueous Na2CO3 and the phases were separated. The aqueous phase was extracted with DCM (3×20 mL) and the combined organics were dried over Na2SO4, filtered, and concentrated. The concentrate was purified by silica gel chromatography (0-20% MeOH in DCM) to provide 6-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)-4-4R)-1-((R)-5-oxopyrrolidin-3-yl)ethoxy)pyrazolo[1,5-a]pyrazine-3-carbonitrile 5.70. LCMS-ESI+ (m/z): [M+H]+ calcd for C26H30N7O3: 488.2; found: 488.0. 1H NMR (400 MHz, Chloroform-d) δ 8.40 (s, 1H), 8.18 (s, 1H), 7.84-7.77 (m, 2H), 7.03-6.96 (m, 2H), 5.99 (s, 1H), 5.64-5.53 (m, 1H), 4.76-4.63 (m, 4H), 3.64-3.51 (m, 2H), 3.50-3.41 (m, 1H), 3.38-3.30 (m, 4H), 3.12-2.97 (m, 1H), 2.60 (dd, J=17.1, 9.2 Hz, 1H), 2.56-2.49 (m, 4H), 2.43 (dd, J=17.1, 8.0 Hz, 1H), 1.54 (d, J=6.2 Hz, 3H).

1. customThe reaction mixture was then partitioned between DCM, water, and 5% (w/v) saturated aqueous Na2CO3
2. customthe phases were separated
3. extractionThe aqueous phase was extracted with DCM (3×20 mL)
4. dry with materialthe combined organics were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe concentrate was purified by silica gel chromatography (0-20% MeOH in DCM)

ORD record

ord-410de2098cb6410abda0a5b6fc0209e0

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376441B2